Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial

Abstract

Objective: This clinical trial investigated the safety and efficacy of single-cycle pembrolizumab in patients with localized deficient mismatch repair (dMMR) colon cancer.

Background: Neoadjuvant immunotherapy has induced remarkable rates of pathological complete response in patients with dMMR colon cancer. However, the optimal length and type of treatment are yet to be determined.

Methods: This was an investigator-initiated, multicenter, single-arm, phase II study (ClinicalTrials.gov: NCT05662527) investigating the safety and efficacy of neoadjuvant pembrolizumab in patients with stage I-III dMMR colon cancer. Patients received a single cycle of pembrolizumab 4 mg/kg (maximum 400 mg) and underwent surgery three to five weeks later. An interim safety and efficacy analysis after including 42 patients was pre-planned. The primary outcomes were safety and efficacy (pathological complete response in more than 20% of patients).

Results: Between February 2023 and September 2023, 42 patients were enrolled at five Danish hospitals. All patients received pembrolizumab and underwent surgery, except one patient who refused to undergo surgery. Surgery was performed a median of 32 days after pembrolizumab treatment. Twenty surgical complications were observed in 16 of 41 patients (39%), three of which were above Clavien-Dindo grade 2. Two were grade 3b, and one was a surgery-related grade 5 gastric ulcer perforation. Three adverse events were grade 3. No grade 4 or 5 adverse events were reported. Of the evaluable patients, 46% (19/41) achieved a pathological complete response, while 61% had a major pathological response.

Conclusion: In conclusion, neoadjuvant single-cycle pembrolizumab was well tolerated and effective in patients with localized dMMR colon cancer. Thus, the inclusion of patients was continued until 85 patients.